_Dr. Eiserich_eiserich-1

_Dr. Eiserich_eiserich-1 - Nitric Oxide: Part I...

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Nitric Oxide: Part I Biosynthesis and Chemical Biology Jason P. Eiserich Department of Internal Medicine School of Medicine University of California, Davis Email: jpeiserich@ucdavis.edu Tel: (530) 752-4010
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Oxidative Stress: What is it? Simply stated: An imbalance between oxidant (radical) production and antioxidant protective mechanisms. antioxidants oxidants
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What is a Free Radical? Hint: Dr. Wu discussed this with you. ..
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An individual who goes through life with both feet planted firmly in the air! - FDR
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“…a free radical is any species capable of independent existence that contains one or more unpaired electrons unpaired electrons .” - Barry Halliwell and John Gutteridge
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“…an unpaired electron is one that occupies an atomic or molecular orbital by itself.” - Barry Halliwell and John Gutteridge
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Diatomic Oxygen: Which are Free Radicals?
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Red uction: gain of electrons by an atom or molecule Ox idation: loss of electrons by an atom or molecule Redox ” Processes
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Biological Sources of Oxidants/Radicals • Mithochondria - electron leak • Xanthine Oxidase • Leukocyte NADPH Oxidases (Respiratory Burst) • Non-Phagocytic NADPH Oxidases (Nox family) O 2 O 2 •- H 2 O 2 •OH Diatomic oxygen Superoxide Hydrogen Peroxide Hydroxyl Radical e - e - (O 2 2- ) e - H 2 O e -
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NO
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Nitric Oxide is a Free Radical
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Timeline of NO Discoveries 1977 - Vasodilators such as nitroglycerin act by releasing nitric oxide 1980 - Vascular relaxation induced by acetocholine and other substances were endothelium dependent (EDRF) 1982 - Correlation between immunostimulation and nitrate synthesis 1983 - Effects of EDRF were determined to be mediated by stimulation of soluble guanylate cyclase with consequent elevation of intracellular cGMP 1985 - EDRF were shown to be inhibited by Hb, methylene blue and other agents - Shortlived substance with a half-life in oxygenated physiological salt solutions 1986 - EDRF effects were prolonged by the addition of SOD and inhibited by Fe++ and hyperoxia 1987 - Identification of EDRF as nitric oxide
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1998 Nobel Prize in Medicine “...discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system”
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NO¥ Protective
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This note was uploaded on 12/30/2010 for the course PMI 285 taught by Professor Wu during the Winter '04 term at UC Davis.

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_Dr. Eiserich_eiserich-1 - Nitric Oxide: Part I...

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